Abstract
For protection from HIV-1 infection, a vaccine should elicit both humoral and cell-mediated immune responses. A novel vaccine regimen and adjuvant that induce high levels of HIV-1 Env-specific T cell and antibody (Ab) responses was developed in this study. The prime-boost regimen that used combinations of replication-competent vaccinia LC16m8Δ (m8Δ) and Sendai virus (SeV) vectors expressing HIV-1 Env efficiently produced both Env-specific CD8+ T cells and anti-Env antibodies, including neutralizing antibodies (nAbs). These results sharply contrast with vaccine regimens that prime with an Env expressing plasmid and boost with the m8Δ or SeV vector that mainly elicited cellular immunities. Moreover, co-priming with combinations of m8Δs expressing Env or a membrane-bound human CD40 ligand mutant (CD40Lm) enhanced Env-specific CD8+ T cell production, but not anti-Env antibody production. In contrast, priming with an m8Δ that coexpresses CD40Lm and Env elicited more anti-Env Abs with higher avidity, but did not promote T cell responses. These results suggest that the m8Δ prime/SeV boost regimen in conjunction with CD40Lm expression could be used as an immunization platform for driving both potent cellular and humoral immunities against pathogens such as HIV-1.
Highlights
An effective HIV vaccine should elicit both antibodies [1] and cell-mediated immune responses in order to control HIV infection
In cells infected with human CD40Lm (hCD40Lm) harboring m8Ds, authentic hCD40Lm protein was produced and cells infected with m8D-pSFJ1-10-hCD40Lm expressed more CD40 ligand mutant (CD40Lm) than those infected with m8D-p7.5-hCD40Lm or m8DEnv/hCD40Lm (Fig. 1B)
A more detailed analysis of IFN-c+ CD107a+ CD8+ T cells by comparison of groups G, H, I and K showed similar results in that m8D-p7.5hCD40Lm co-immunization with m8D-Env increased the number of functional CD8+ T cells. These results indicate that the m8D prime and Sendai virus (SeV) boost regime efficiently elicits Env-specific cellular immunity, and that the inclusion of hCD40Lm delivered by a separate vector enhances cellular immunity elicited by m8D-Env
Summary
An effective HIV vaccine should elicit both antibodies [1] and cell-mediated immune responses in order to control HIV infection. Adenovirus and vaccinia virus-based vectors expressing Gag, Nef, and other components of HIV-1 have been shown, in nonhuman primates [2,3,4,5] and in human trials [6,7], to elicit considerable multifunctional T cell responses and control early viral replication to some extent. These preparations, did not induce a sufficient level of immunity to protect vaccinees from HIV/simian immunodeficiency virus (SIV) infection in the absence of neutralizing antibodies [8]. More potent immunogens and better vaccination regimens are required
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